Modern texts locate the primary pacemakers of the heart in the sinoatrial node (SAN) along the superior end of the sulcus terminalis extending to the junction of the superior vena cava and right atrium. It is also generally assumed that the artioventricular nodal region (AVN) is the next most excitable pacemaker region once the SAN is damaged or destroyed. Our experience however, locates subsidiary atrial pacemakers (SAP) along the sulcus (crista) terminalis in the canine right atrium. These pacemakers assume the dominant pacemaker role in the absence of SAN in chronic preparations. This proposal describes three projects designed to characterize and compare functions of SAP with those of SAN and AVN pacemakers. Project I will compare responses of SAN (before) and SAP (after) surgical excision of the SAN region of the dog heart. Physiological testing will consist of responses to direct Beta-adrenergic stimulation (isoproterenol) and blockade (propranolol), cholinergic block (atropine), and rapid atrial pacing, all in the same animals, before and at regular intervals after surgical extirpation of the SAN (SAN-X). In a second group of dogs, graded lengths of the sulcus (crista) terminalis will be excised in addition to SAN, with electro-physiological localization of the dominant pacemaker regions in the alert, conscious animal. Autonomic innervation of the SAP has been demonstrated in preliminary experiments, but the role of these neural influences in assumption of pacemaker dominance after SAN-X remains totally unknown. Thus pacemaker location and function will be examined in the chronic dog model before and after SAN-X after (1) total, intrapericardial cardiac denervation, (2) after cardiac sympathectomy (parasympathetics remaining intact), and (3) after cardiac parasympathectomy (sympathetics intact). Technologies essential to the performance of selective differential denervation are immediately available in this laboratory. 24-hour monitoring (Holter) of the ECG in normally performing dogs during exercise, atropine, propranolol, and isoproterenol regimens will permit comparisons in functional behavior of SAN, SAP, and AVN pacemaker tissues before and after SAN-X. Rapid atrial pacing at systematically altered rates in the same conscious animals will permit similar comparisons in overdirve suppression and overdrive excitation.